It is proposed to initiate an integrated pharmacological and biochemical study on the molecular basis of the carcinogenic activity of dioxane and related compounds, and for the development of means of pharmacological protection against chronic exposure in an industrial environment. The study will explore in depth the distribution (tissular and subcellular) and metabolism-dependent macromolecular binding of dioxane in vivo and in vitro, the effect of microsomal enzyme inducers and repressors on this binding, as well as on dioxane metabolism. In another phase of this study, the structure of the activated, reactive carcinogenic form of dioxane will be elucidated. Again, in another phase the effect of dioxane under chronic, carcinogenic conditions on DNA, RNA and protein synthesis in the target tissues will be studied. Included in this proposal is an exploration of the structure versus carcinogenic activity relationship of analogs and derivatives of dioxane, and effect of inducers and repressors of microsomal metabolism as well as of dietary variables on the carcinogenicity of dioxane. It is also planned to investigate the possible embryotoxicity and teratogenicity of dioxane.